Methods of making bioprosthetic heart valves with strain matched leaflets

ABSTRACT

Heart valve leaflet selection methods and apparatuses which subject individual leaflets to loads and measure the resulting deflection to more reliably group leaflets of similar physical characteristics for later assembly in prosthetic heart valves. The deflection testing may be accomplished using a variety of test set ups which are designed to impart a load on the leaflet which simulates the actual loading within a heart valve. The results from a number of deflection tests are used to categorize individual leaflets, which data can be combined with other data regarding the characteristics of the leaflet to better select leaflets for assembly into a multi-leaflet heart valve. In one embodiment, the deflection test is combined with an intrinsic load test, and leaflets having similar deflection and intrinsic load values used in the same heart valve. One apparatus for testing the leaflets includes a frame for securing the arcuate cusp of the leaflet while the straight coapting edge remains free, to simulate the actual leaflet mounting configuration within the heart valve prosthesis. The frame may include a lower portion having a recess for the leaflet and plurality of receptor holes around the peripheral edge of the recess, and an upper portion having a plurality of needles which extend downward through the leaflet and into the receptor holes and secure the edges of the leaflet.

RELATED APPLICATIONS

The present application is a continuation of Ser. No. 10/140,085 filedMay 7, 2002 now abandoned, which is a continuation of Ser. No.09/710,409, filed Nov. 13, 2000 now U.S. Pat. No. 6,413,275 which is adivisional of Ser. No. 09/207,783, filed Dec. 9, 1998, now U.S. Pat. No.6,245,105, which is a divisional of Ser. No. 08/833,176, filed Apr. 3,1997, now U.S. Pat. No. 5,961,549.

FIELD OF THE INVENTION

The present invention relates to prosthetic heart valves, and moreparticularly to prosthetic heart valves comprised of leaflets that havebeen strain tested and sorted according to strain response.

BACKGROUND OF THE INVENTION

Prosthetic heart valves are used to replace damaged or diseased heartvalves. In vertebrate animals, the heart is a hollow muscular organhaving four pumping chambers: the left and right atria and the left andright ventricles, each provided with its own one-way valve. The naturalheart valves are identified as the aortic, mitral (or bicuspid),tricuspid, and pulmonary valves. Prosthetic heart valves can be used toreplace any of these natural valves. The two primary types of prostheticheart valves known in the art are mechanical valves and bio-prostheticvalves. Mechanical valves include rigid leaflets and a pivotingmechanism, and bio-prosthetic valves utilize flexible tissue leaflets,typically mounted to a manufactured support frame. The present inventionprovides methods for selecting leaflets in bio-prosthetic valves.

Bio-prosthetic valves may be formed from an intact, multi-leafletporcine (pig) heart valve, or by shaping a plurality of individualleaflets out of bovine pericardial tissue and combining the leaflets toform the valve. The pericardium is a sac around the heart of vertebrateanimals, and bovine (cow) pericardium is commonly used to makeindividual leaflets for prosthetic heart valves. The bovine pericardiumis first harvested from the animal and then chemically fixed tocrosslink collagen and elastin molecules in the tissue and increase thetissue durability, before being cut into leaflets. Various physicalcharacteristics of the tissue may be examined before or after fixation.

One drawback faced by a patient having an implanted bio-prosthetic heartvalve is the potential for calcification of the leaflets if the valveremains in place for an extended period of time (more than ten years).Calcification tends to make the leaflets less flexible. A significantamount of research has been accomplished in mitigating calcification ofbovine pericardial leaflets to lengthen the useable life of the heartvalve. Calcification may reduce the performance of the heart valve, andthus, the highest quality materials and design in the heart valve isrequired to forestall a failure of the valve from excessive calciumdeposits.

Despite the drawbacks of artificial heart valve material, over twentyyears of clinical experience surrounding implanted artificial heartvalves has produced a proven track record of success. Research inextending the useful life of the bio-prosthetic valves continues,however. One aspect of designing heart valves which is very important inimproving their performance is the selection of the pericardial tissueused in the leaflets. In all heart valves, the natural action of theflexible heart valve leaflets, which seal against each other, or co-apt,is desirable. The difficulty in simulating the leaflet movement of anactual heart valve (especially a mitral salve) in a prosthetic valve isthat the leaflets used are “inanimate.” There are no muscularattachments to the leaflets as in the natural valve, and the prostheticleaflets must co-apt to function properly solely in response to thefluid pressures within the heart chambers. Indeed, natural coaptation ofthe leaflets in bio-prosthetic valves comprising a plurality ofindividual leaflets sewn together is particularly difficult, even whencompared to inanimate but intact valves, such as harvested porcinevalves.

Much of this research involves the mechanical properties of fresh orfixed bovine pericardium. A good discussion of the various physicalproperties of fixed bovine pericardium is given in Simonescu, et al,Mapping of Glutaraldehyde-Treated Bovine Pericardium and TissueSelection For Bio-prosthetic Heart Valves, Journal of Bio-MedicalMaterials Research, Vol. 27, 1993. Simionescu, et al, recognized thesometimes striking variations in physical properties of the pericardialtissue, even in the same pericardial sac. Their research mapped outareas in individual pericardial sacs and tested those areas for fiberorientation, suture holding power, and thickness. In another paper bySacks, Bi-axial Mechanical Behavior of Fixed Bovine Pericardium, FifthWorld Biomaterials Congress, May-June 1996, the collagen fiberarchitecture within bovine pericardial tissue was examined and variousspecimens were tested in a bi-axial tester. The results indicated thatby presorting for uniform collagen fiber architecture, more uniformbio-pericardial specimens could be obtained for better controlled use inbioprosthetic applications. Finally, in another study, Zioupos, et al,Anisotropic Elasticity and Strength of Glutaraldehyde Fixed BovinePericardium For Use In Pericardial Bioprosthetic Valves, Journal ofBiomedical Materials Research, Vol. 28, 1994, various tests wereperformed on fixed bovine pericardial tissue to determine thestress/strain behavior along various axes. The results suggest thatleaflets can be made from fixed bovine pericardium possessing pronouncedanisotropy in strength and stiffness along two orthogonal directions. Inthe leaflets circumferential direction, which bears most of the stressduring function, the stiffer pericardium is desired, while in the radialdirection, more flexible tissue is desired. Leaflets are thus cut frombulk tissue whose properties have generally been examined, and theleaflets categorized accordingly.

Despite the extensive research into bulk tissue characteristics thereremains a need for a more reliable method of selecting leaflets toinsure maximum functional compatibility with the other leaflets in thedynamic operating environment of a prosthetic heart valve.

SUMMARY OF THE INVENTION

The present invention provides methods and apparatuses for selectingleaflets for use in producing multi-leaflet prosthetic heart valves. Theselection of leaflets to be combined in a heart valve is based ongrouping a plurality of leaflets by strain response to an applied loadwhich is designed to simulate physiological pressures within the heart.A stress load sufficient to stress the leaflets within a high modulusregion of their stress/strain characteristic is applied to each leaflet,and leaflets within a predetermined observed deflection range of eachother are grouped together. In an exemplary embodiment,glutaraldehyde-fixed leaflets are stressed within a generally linear,high modulus region of the bulk tissue stress/strain curve, and thedeflection measured for grouping the leaflets. In one embodiment, thestrain response is observed relative to a deflection of bovinepericardium leaflets resulting from applying a load thereto, and two orthree leaflets from a group of leaflets having deflections within 0.030inches of each other are combined to form a prosthetic heart valve

One aspect of the present invention is a method of selecting leafletsfor an implantable heart valve, including providing a collection ofsimilarly sized leaflets, applying a load to each leaflet, observing theresulting strain response, and sorting the leaflets based on theirrespective strain responses. The collection may be natural tissueleaflets which are chemically fixed prior to testing. The natural tissueleaflets may be made of bovine pericardium. In one embodiment, the loadapplied is sufficient to create an average stress in at least some ofthe leaflets of between 300 and 600 kPa. The load is preferably appliedfor a predetermined number of times prior to observing the strainresponse. Another aspect of the invention is a bioprosthetic heart valvemanufactured with leaflets selected by the aforementioned method,wherein the number of leaflets selected may be three.

The present invention also provides a method of testing a leaflet foruse in an implantable heart valve, including mounting the leaflet in aframe so that portions which are to be sutured in the valve are heldstationary. A load is applied to the leaflet in a location adapted tosimulate a point at which an average load is applied in the valve, andthe resulting strain in the leaflet is sensed. The natural tissueleaflet typically defines a cusp and a coapting edge generally oppositethe cusp, and the step of mounting may comprise holding stationary atleast the cusp of the leaflet. The leaflet may be positioned in aframing assembly having a recess for receiving at least the edges of thecusps of the leaflet, and a cavity circumscribed by the recess.Moreover, the load may be applied by a mechanical deflector to an uppersurface of the leaflet over the cavity. Preferably, the framing assemblyincludes an upper member and a lower member, the lower member having therecess and the upper member shaped to mate over the recess. The methodfurther includes piercing the leaflet edges with needles extendingbetween and supported from movement by the upper and lower members.

The present invention provides an apparatus for testing heart valveleaflets having a leaflet framing assembly including a holder with arecess for receiving a leaflet to be tested and a frame which cooperateswith the holder to hold stationary the cusps of the leaflet. Theapparatus includes a base having indexing structure for locating theframing assembly thereon, and a deflection assembly indexed with respectto the base and having a deflector mounted for movement above theframing assembly to contact the leaflet. The recess may be cusp-shaped,and the holder includes a cavity substantially surrounded by the recessover which the leaflet is suspended. The apparatus may further includestructure adapted to hold stationary discrete points of the leafletaround the cavity. To secure discrete points of the leaflet around thecavity, the frame preferably includes a plurality of needles havingtheir pointed ends downward, and the recess includes receptor holes forthe needles, wherein the cusp of the leaflet is secured against movementat the discrete points defined by the needles.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a front perspective view of an exemplary leaflet testerillustrating the principles of the present invention;

FIG. 2 is a rear perspective view of the leaflet tester of FIG. 1;

FIG. 3 is a perspective view of a leaflet mounting frame for use in theleaflet tester;

FIG. 4 is an exploded perspective view of the leaflet mounting frame anda needle calibration gauge for use therewith;

FIG. 5 is a perspective view of an exemplary leaflet holder for use inthe leaflet tester;

FIG. 6 is an exploded perspective view of the leaflet mounting frameover the leaflet holder, with a leaflet held therein;

FIG. 6 a is a top elevational view of the leaflet holder, with leaflettherein, taken along line 6 a—6 a of FIG. 6;

FIG. 7 is an assembled perspective view of a leaflet framing assemblycomprising the leaflet mounting frame, and leaflet holder;

FIG. 8 a is an elevational view of a deflector in contact with a leafletto be tested and mounted within the framing assembly prior to adeflection test;

FIG. 8 b is a front elevational view of the framing assembly with aleaflet support removed and the deflector deflecting a leaflet;

FIG. 9 is a graph showing tissue deflection values for a plurality of 29mm CEP mitral valve leaflets;

FIG. 10 a is a graph showing a distribution of deflection values for anumber of leaflets which have been previously grouped and categorized bydroop characteristic, Category A;

FIG. 10 b is a graph showing a distribution of deflection values for anumber of leaflets which have been previously grouped and categorized bydroop characteristic, Category B;

FIG. 10 c is a graph showing a distribution of deflection values for anumber of leaflets which have been previously grouped and categorized bydroop characteristic, Category C.; and

FIG. 11 is a graph illustrating a typical stress-strain curve forpericardial tissue.

DESCRIPTION OF THE EXEMPLARY EMBODIMENTS

The present invention involves testing individual leaflets for use inproducing heart valves which, in its broadest sense, provides methodsand apparatuses for obtaining and grouping the deflection response ofindividual leaflets in order to better sort or group them for laterselection and combining with other leaflets to form a valve. Unlikeprior art bulk tissue testing, the present invention characterizesindividual leaflet response under loads similar to those the leafletsare subjected to under normal physiological conditions within the heart.Not only are the loads higher than previously used in tissue testing,but the leaflets are subjected to repeated loadings, which conditionsthe leaflet tissue, prior to observing a deflection. Although the bulkmechanical properties of tissue in general have been studied, prior artnon-destructive tests of individual tissues already cut to leaflet shapehave not been developed or utilized to group tissue leaflets forassembly into prosthetic valves.

An exemplary deflection testing apparatus, disclosed within theteachings of the present invention, closely simulates dynamic pressureon the individual leaflets with a mechanical deflector having a smooth,generally spherical tip on the end for repeatedly contacting a framedand supported leaflet at a pre-determined contact location. The leafletis framed and secured around its periphery at a number of discretepoints designed to simulate the lines of suturing that would retain theleaflet within an actual prosthetic heart valve. The invention shouldnot be limited to the specific apparatus shown, however, and is intendedto cover any equivalent apparatuses or methods which take individualleaflets and subject them to loading while measuring their deflectionresponse. For example, an alternative apparatus contemplated as beingwithin the scope of the present invention may apply a pressure to theleaflet, as opposed to a discrete or diffuse mechanical load.

Exemplary Deflection Tester Apparatus

One particular embodiment of a leaflet deflection tester 20 for loadingindividual leaflets is shown in FIGS. 1 and 2. Referring to FIG. 1, theleaflet deflection tester 20 comprises a flat base 22 supporting aleaflet framing assembly 24 and a deflector assembly 26 thereabove. Aleaflet 28 is shown mounted within the framing assembly 24 and adeflector 30 is positioned to apply a load to the leaflet to result in adeflection which can be read from display 32. For purposes ofdiscussion, the display 2 faces in a forward longitudinal direction, andlateral left and right directions are defined from the perspective oflooking at the display.

The deflector assembly 26 comprises a support post 34 verticallyoriented with respect to the base 22 and attached thereto with a postholder 36. Referring to FIG. 2, at the top of the post 34, a cap 38 isvertically adjustable via a set screw 40 engaging a vertical groove 42in one side of the post. An indicator carriage 44 is also verticallyadjustable along the post and may be secured at various locations usinga pair of carriage locking screws 46 which also engage the groove 42. Acarriage arm 48 extends longitudinally forward from the post 34 andterminates in a position indicator 50 mounted thereto. Referring to FIG.1, the position indicator preferably includes electronic circuitry and adigital readout 32, but may be of a variety of configurations, and theparticular embodiment illustrated herein should not be construed aslimiting. Control buttons 51 including a zero reset function areprovided on the face of the indicator 50.

The position indicator 50 is generally centrally located above theleaflet framing assembly 24 and includes an indicator shaft 52,vertically passing therethrough and engaging position-sensing equipmentwithin the indicator. That is, various known mechanical orelectro-mechanical devices for sensing the displacement of a shaftwithin a housing are contemplated for this purpose and will not bedescribed further herein. A mass 54 attaches to an upper end of theindicator 52 above the position indicator 50. At the lower end of theshaft 52, a collar 56 is fastened thereon via a locking screw 58. Thecollar continues downward and terminates in the aforementioned deflector30.

The deflector assembly 26 further includes a means for verticallyadjusting the position between the post cap 38 and the indicatorcarriage 44. A vertical adjustment knob 60 is mounted for rotation abovea vertical axis through the post cap 38. The adjustment knob 60 engagesa connecting rod 62 which extends between the post cap 38 and theindicator carriage 44. In one embodiment, the vertical adjustment knob60 rotates a threaded nut within the post cap 38 which engages malethreads on an upper end of the connecting rod 60 to cause its verticaldisplacement. The connecting rod 62 is preferably firmly connected tothe indicator carriage 44 and thus turning the vertical knob 60vertically displaces the indicator carriage 44. The use of the verticaladjustment knob 60 in calibrating and operating the tester 20 will bedescribed below.

With reference still to FIG. 1, and, more particularly, to the rearperspective view in FIG. 2, the post holder 36 is formed as a monolithicT-shaped block, having a pair of overhanging edges through whichlongitudinally oriented adjustment slots 68 are provided. The slots 68are provided on either lateral side of the support post 34 and receivelocking bolts 70 which extend downward into engagement with a step 72formed in a longitudinal adjustment bracket 74. The longitudinaladjustment bracket 74 can thus be adjusted longitudinally with respectto the post holder 36 and secured with the bolt 70.

On a front end of the longitudinal adjustment bracket 74, an overhangingportion includes a lateral adjustment slot 76 receiving a locking screw78. Referring to FIG. 1, the locking screw 78 continues through theoverhanging portion of the adjustment bracket 74 into contact with astep 80 formed in a lateral adjustment bracket 82 which is generallyL-shaped, having a forwardly extending arm portion 84. An L-shaped clamp86 is adjustable longitudinally with respect to the arm portion 84 andis fastened thereto with a pair of clamping screws 88. The combinationof the adjustment brackets 74 and 82, and L-shaped clamp 86, index andsecure the leaflet framing assembly 24 with respect to the support post34 and, in turn, the position indicator 50.

An upper framing assembly member or leaflet mounting frame 94,illustrated in FIGS. 3 and 4, comprises a generally rectangular shapedbase 96, having an upper stepped recess 98 open to a front side of therectangle. An undercut 100 is formed in the recess 98 to receive aplate-shaped needle clamp 102 therein. The needle clamp 102 includes asemicircular cutout 104 in an edge facing toward the open edge of therecess 98. The cutout 104 conforms to a semicircular cutout 106 formedin the base 96. It should be noted that although the cutouts 104, 106are described as generally semicircular, the particular shape of theleaflet 28 may be somewhat oval in shape, which may correspondinglyalter the shape of the cutouts.

Both the base 96 and the needle clamp 102 include a plurality ofregistered, vertical through holes 108, arranged equidistantly aroundthe semicircular cutouts 104 and 106. In a preferred embodiment, thereare seven such through holes 108, arrayed at specific circumferentialangles around the cutouts 104 and 106. The through holes 108 receiveleaflet framing needles 110 which are vertically retained thereinthrough the use of a needle clamp screw 112 threaded through a rear wallof the frame body 96 and into contact with the needle clamp 102.

The frame base 96 further includes a plurality of positioning tabs 114depending downward therefrom. In the illustrated embodiment, there arethree such tabs 114, two on left and right sides, respectively, of theframe base 96 and one on the rear side. With reference to FIG. 4, thetabs are utilized to orient a needle gauge or calibration member 116under the cutouts 104 and 106. More particularly, the needle gauge 116comprises a generally rectangular base 118 and a recessed pocket 120.The base 118 is guided between the two side tabs 114 and abuts againstthe rear tab of the mounting frame 94. In this orientation, the pocket120 is positioned directly below all of the through holes 108 so thatthe needles 110 depend downward below the lower surface of the framebase 96, as seen at 122, only as far as the pocket. The needles 110 areinserted through the holes 108 into contact with the pocket 120, andthen the needle clamp screw 112 is tightened to push the needle clamp102 in a direction out of the recess 98 and create a compression againstthe needles 110. That is, the shear force exerted on the needles 110 bythe through holes 108 in the frame base 96 and needle clamp 102maintains the needles in the vertical position as calibrated by theneedle gauge 116. Once the needles are calibrated to depend downward thesame distance, the frame 94 is ready for use in the framing assembly 24.

FIG. 5 illustrates a lower framing assembly member or leaflet holder 126comprising a block-shaped body 128 having a flat lower surface adaptedto rest on the base 22 (FIG. 1) and a flat upper platform 130. The body128 is generally rectangular in shape and includes a rectangular baselocator 132 projecting from a front side and shorter in height than thebody 128. The outer edges of the body 128, other than the edge fromwhich the base locator 132 extends, include positioning channels 134opening to the platform 130. The positioning channels 134 receive thepositioning tabs 114, previously described for the leaflet mountingframe 94, as best seen in FIG. 6, to locate the mounting frame withrespect to the leaflet holder 126. The lower surface of the leafletmounting frame base 96 is flat and is juxtaposed with the flat platform130. In the center of the body 128, and opening toward the base locator132, a cavity 136 is formed having a generally semicylindrical shape. Astepped leaflet edge recess 138 is formed in the platform 130surrounding the cavity 136 and is sized and shaped to receive a leaflet,such as the leaflet 28 as shown in FIGS. 1 and 2.

Referring to FIG. 5, a paddle-shaped leaflet support 140 has a generallysemicircular end which fits closely within the cavity 136, with a handle142 extending outward from the cavity 136 and resting on a top surfaceof the base locator 132. The leaflet support 140 has a height which isidentical to the height from the top surface of the base locator 132 tothe elevation of the leaflet edge recess 138 so that the upper surfaceof the leaflet support 140 is in the same plane as the edge recess 138.The edge recess 138 further includes a plurality of needle receptorholes 144 sized and positioned in an array identical to the array inwhich the through holes 108 and associated needles 110 are positionedaround the leaflet mounting frame 94. This arrangement allows theneedles 110 to extend through the peripheral edge of the leaflet 28 intothe receptor holes 144, thus holding stationary portions of the leafletat the edge recess 138.

With reference to FIG. 6 a, the leaflet typically includes a straightcoapting edge 148 having opposed tab ends 150, and a generallysemicircular cusp 152 therebetween and opposite the coapting edge. Thetab ends 150 include angled sides 153 transitioning to the coapting edge148. The edge recess 138 is sized and shaped to receive the cusp 152 andtabs 150 with the coapting edge 148 oriented parallel with but spacedfrom a front edge of the holder 126.

FIG. 6 a also illustrates a point 154 at which an axis through thecenter of the deflector 30 intersects the leaflet 28. This point 154will be referred to herein as the point of contact between the deflector30 (FIG. 1) and leaflet 28, but in the exemplary embodiment thedeflector is a relatively large diameter smooth hemisphere, and contactsthe leaflet over a circular area to better simulate a distributed loadand to help avoid stress risers. The point 154 is determined from amodel of the stress distribution in the leaflet based on assumed forcesapplied to the leaflet in a human heart valve. The forces applied to theleaflet in a human heart valve originate from fluid pressures upstreamand downstream of the valve, and the stress distribution is found fromthe leaflets' shape and boundary conditions (i.e., geometry of the linesof sutures attaching the leaflets in the valve). The point 154 is thusan idealized concentrated load point (or concentrated area) equivalentto the actual distributed pressure load.

The leaflet is symmetrical about an axis perpendicular to and bisectingthe coapting edge 148, and is typically continuously sutured in anactual valve along the cusp 152, and thus the point 154 is desirably onthat axis. The dimension “A” is the distance from the point 154 to thecoapting edge 148 determined from the aforementioned stress distributionmodel. The dimension “A” will vary depending on the size and geometry ofthe leaflet, its thickness and bulk material properties, and the assumedstress distribution. It will be noted, however, that the point 154 isspaced from the coapting edge 148, which prevents undue tensile stressesbetween the deflector 30 and the points closest to the coapting edge atwhich the leaflet is held stationary in the framing assembly 24 (i.e.,needles 110, as will be described below). The particular apparatus andmethods disclosed, and the concentrated loading, requires that the point154 be spaced from the coapting edge 148 to best distribute the tensilestresses between the deflector 30 and the stationary points at theleaflet periphery. Of course, those of skill in the art will recognizethat a more accurate test setup with actual suturing around the cusp 152and a pressure loading over the surface of the leaflet could besubstituted within the scope and teaching of the present invention, andthe presently illustrated test setup is an approximation driven bypractical manufacturing considerations.

The interaction of the leaflet mounting frame 94 with the leaflet holder126 will be explained with reference to FIG. 6 and 7. As mentioned, thepositioning tabs 114 fit within the positioning channels 134 to orientthe mounting frame 94 with respect to the leaflet holder 126. Theregistration between the tabs 114 and channels 134 insures that theneedles 110 in the through holes 108 in both the base 96 and needleclamp 102 of the mounting frame 94 align with the needle receptor holes144 in the leaflet holder 126. The assembly arrow 146 illustrates themovement of the mounting frame 94 when coupling to the leaflet holder126. In an anticipated alternative embodiment, the mounting frame 94will be hingedly or otherwise pivotally coupled to the holder 126, withthe final relative movement being vertical to avoid skewing the needleswithin the receptor holes 144.

The leaflet 28 is pre-positioned so that its outer edges conform to theshape of the leaflet edge recess 138, and the middle portion issupported by the leaflet support 140. The needles 110 extending downbelow the leaflet mounting frame 94 thus pierce and pass through thetissue of the leaflet 28 and extend into the receptor holes 144. In aheart valve, the cusps 152 of each leaflet are supported by a wireform,and the coapting edges 148 remain free to cooperate with the coaptingedges of the other leaflets. The framing assembly 24 thus closelysimulates the static points of attachment so that the stressdistribution, and accompanying deflection response, in the leaflet 28 isas near to the actual distribution as possible. The needles 110 holdstationary peripheral portions of the leaflet 28 to approximate anactual line of sutures peripherally securing the leaflet within a heartvalve. Furthermore, the lower surface of the mounting frame base 96rests on the upper surface of the platform 130. In this regard, it isimportant to note that the leaflet 28 is preferably not compressed, oronly lightly compressed, by the weight of the mounting frame 94 becauseit is positioned within the recess 138. The final assembled leafletframing assembly 24 is illustrated in FIG. 7.

FIGS. 8 a and 8 b illustrate two positions of the deflector 30 during aleaflet deflection test. The leaflet 28 is mounted in the framingassembly 24 with the leaflet support 140 supporting the leaflet 28 fromunderneath in a plane at the same elevation of the leaflet edge recess138, and thus the leaflet 28 does not bend or sag in its mid-portion.The deflector 30 is lowered into a position just contacting the top ofthe leaflet 28, as shown in FIG. 8 a, prior to a deflection test.Subsequently, the leaflet support 140 is removed from underneath theleaflet 28, and the indicator shaft 52 is allowed to drop as in FIG. 8b, thus causing the deflector 30 to displace the leaflet 28 until anequilibrium is reached. The equilibrium depends on the framing geometry,the size of the mass 54 (FIG. 1), and the stress/strain characteristicsof the leaflet 28. The total deflection of the leaflet at the point ofcontact with the deflector 30 is illustrated in FIG. 8 b by thedimension “d”. As described below in the Exemplary Test Assemblysection, an approximate measurement of the true deflection “d” is madeby disregarding the relaxed thickness of the leaflet being tested forsimplicity of calibration of the apparatus and method.

Preferably, the deflector 30 is a relatively large diameter smoothhemisphere so that the load imposed on the upper surface of leaflet 28is somewhat distributed. The deflector 30 is made of a biocompatiblematerial, such as a plastic, and preferably a thermoplastic. Othervariations of deflector 30 are envisioned and the present inventionshould not be construed to be limited to the illustrated embodiment. Forexample, a more uniformly distributed load such as a pressure load maybe imposed upon the leaflet 28 and the subsequent deflection measured.In all cases, the aim is to closely simulate the conditions experiencedby the leaflet 28 in an actual heart valve. Indeed, it would bedesirable to load test leaflets after being installed on a heart valvewireform and support ring. However, even if such a test could beaccurately configured, it would be difficult to test individual leafletswithin a three leaflet prosthetic valve, for example. Furthermore, oncethe valve has been constructed, many of the benefits of the leafletselection process are rendered moot. That is, the primary considerationis finding similar leaflets to combine within a single heart valve. Asecondary consideration, which is not insignificant, is being able toselect a leaflet prior to construction of the valve to reducemanufacturing time and expense. Construction of a heart valve involvesmany intricate steps of sewing leaflets together and to the wireform andsurrounding fabric covering. The work must be done by highly skilledtechnicians and thus testing of individual leaflets within fullyconstructed valves is prohibitively expensive, although not outside ofthe scope of the present invention.

The present invention thus seeks to provide a selection method forindividual leaflets prior to construction of a heart valve which mostaccurately predicts the ultimate mechanical response of each leafletwithin the constructed valve and ensures optimum performance incoaptation with the other leaflets. To that end, the presentlyillustrated test apparatus 20 is believed to closely simulate the forcesand stresses imposed on the leaflet during use, in a relatively easy toset up and operate environment. Because of the modular nature of thetest apparatus 20, repeatability of tests for various sizes of leafletsis enhanced. That is, the leaflet holder 126 is sized for a particulardiameter of leaflet, and a number of leaflet holders having differentleaflet edge recesses 138 may be provided for different sized leaflets.The external dimensions of the leaflet holder 126 remain the same sothat it may be indexed within the aforementioned brackets on theplatform 22 (FIG. 1) and the same deflection assembly 26 is utilized.Concurrently, the leaflet mounting frame 94 may be provided in a varietyof sizes to cooperate with different sized holders. An additionaladvantage is the relatively small size and portable nature of the tester20. The platform 22 may be set up on assembly lines, laboratory tables,and even desktops.

Exemplary Test Assembly

The steps in preparing the exemplary tester apparatus 20 for use willnow be described with respect to the drawings. First of all, theequipment is cleaned to remove any particulate matter and dirt adheredthereto. The test equipment is then sterilized through a processincluding a bio-burden reduction process (BREP) well known in the art.

With reference to FIGS. 1 and 2, the post cap 38 is first secured on thepost 34 by tightening the set screw 40. The locking screws 46 areloosened to allow the carriage 44 to freely move vertically on the post34. Additionally, the locking bolts 70, locking screws 78, and clampingscrews 88 are loosened. Prior to installing the leaflet framing assembly24, the framing assembly 24 must be indexed under the deflector assembly26. To accomplish this, an indexing tip (which is not shown) is fastenedto the lower end of the indicator shaft 52 in place of the collar 56 anddeflector 30. The indexing tip on the lower end of the indicator shaft52 fits through an indexing hole (not shown here) within the cavity 136formed in the leaflet holder 126. The indexing hole allows the indexingtip to contact the platform base 22. Once the indexing tip has contactedthe base 22, the carriage locking screws 46 are tightened to locate thecarriage 44. As the indexing hole is sized just large enough to receivethe indexing tip, the leaflet holder 126 is located in its properposition with respect to the position indicator 50. That is, thevertical axis of the indicator shaft 52 is positioned at the preciselocation with respect to the leaflet holder 126 so that the deflector30, when eventually installed, will contact the leaflet 28 in the properposition.

The longitudinal adjustment bracket 74 and lateral adjustment bracket 82are then manipulated to contact the framing assembly 24 under thedeflector assembly 26. The longitudinal adjustment bracket 74 andlateral extending portion of the lateral adjustment bracket 82 aredisplaced to contact the associated sides of the leaflet holder 126, andthe arm portion 84 contacts the end of the base locator 132. The lockingbolts and locking screw 78 are tightened. The carriage locking screws 46are then loosened and the vertical adjustment knob 60 manipulated toraise the carriage 44 upward. The indexing tip is removed.

The correct size deflector 30 is chosen depending on the size of theleaflet 28 to be tested. The collar 56 of the deflector 30 is attachedto the lower end of the indicator shaft 52 via the locking screw 58.Next, the proper size mass 54 is selected for the leaflet 28 to betested. In this regard, a single mass for a particular size of leaflet28 is preferred, although different masses may be used on the sameleaflet for a variety of deflection results. The mass 54 must beselected so as not to over stress the leaflet 28 being tested. Thus, forexample, stress loading for a glutaraldehyde-fixed pericardial tissueleaflet within a mitral valve is up to 1,000 kPa. For this application,therefore, the mass 54 should be chosen so that the stress imparted tothe leaflet 28 is no greater than 1,000 kPa.

At this point, the position indicator 50 is calibrated. With the leafletsupport 140 in position, the position indicator 50 is reset so that thedisplay 32 reads zero, using one of the control buttons 51. The carriagelocking screws 46 are then loosened and the entire position indicator 50is lowered using the vertical adjustment knob 60 on the top of the postcap 38. The carriage 44, along with the position indicator 50, islowered until the deflector 30 contacts the upper surface of the leafletsupport 140. The vertical adjustment knob 60 is further turned to lowerthe position indicator 50 while the indicator shaft 52 remainsstationary until the display 32 reads a deflection of betweenapproximately 0.390″ and 0.410″. Then the carriage locking screws 46 aretightened to lock the position indicator 50 in place.

The display 32 is then again set to a zero reading, using one of thecontrol buttons 51. This sequence ensures that the deflector 30 can dropa sufficient distance below the level of the leaflet support 140 toensure the leaflet under test is properly stressed (i.e., notunderstressed). That is, a proper deflection reading is desirablyobtained within a nearly linear, high modulus region of the particularleaflet stress/strain curve, prior to reaching the yield stress, asdescribed below with reference to FIG. 11. In general, the optimumstress level is first approximated, and the mass and total allowabledeflection selected accordingly from that approximation to result instress in a linear region of the tissue stress/strain curve.

It should be noted that the leaflet deflection is measured from a zerodatum of the top of the leaflet support 140, and the thickness of theparticular leaflet is disregarded. The leaflet thickness is relativelysmall in comparison to the deflection, and the ultimate test results areused to compare leaflets, so the slight inaccuracy from not taking theleaflet thickness into account applies to all of the leaflets, and isthus rendered even less important. Thus, the dimension “d” indicated inFIG. 8 b is the true deflection, while the deflection actually measuredis off by the relaxed thickness of the leaflet being tested, and is aclose approximation of the true deflection.

The next step in the test preparation process is to secure the leaflet28 within the framing assembly 24. First, the leaflet mounting frame 94is assembled by inserting the needle clamp 102 in the base 96. Asmentioned previously, the appropriately sized base 96 and needle clamp102 are chosen for the particular leaflet 28 being tested. The needles110 are inserted into the through holes 108, until their tips justextend beyond the lower surface of the base 96 as seen in FIG. 4. Ofcourse, throughout this operation, the needle clamp screw 112 is looseto remove any shear force between the needle clamp 102 and the base 96.

As shown in FIG. 4, the leaflet mounting frame 94 is then positionedover the needle gauge 116 on a flat surface and the needles 110 allowedto drop until their lower tips contact the upper surface of the pocket20. At this stage, the needle clamp screw 112 is tightened to apply ashear between the needle clamp 102 and the base 96, which holds theneedles 110 in their calibrated elevation. The needles 110 areindividually pulled to insure that they are tightly held in the properposition and if any of the needles move, the needle clamp screw 112 isrecalibrated and tightened further. Before placement of the leaflet 28within the leaflet holder 126, the leaflet mounting frame 94 is firstpositioned over and mated with the leaflet holder to insure that theneedles 110 register with and extend freely into the receptor holes 144.The mounting frame 94 is then removed from the leaflet holder 126.

The leaflet support 140 is then installed in the cavity 136 of theleaflet holder 126, and the leaflet 28 to be tested positioned on theleaflet support so that its peripheral edges conform to theappropriately sized leaflet edge recess 138. The mounting frame 94 isthen brought vertically over the leaflet holder 126 and displaceddownward so that the needles 110 pass through the tissue of the leaflet28 and into the receptor holes 144. In its assembled state, as shown inFIG. 7, the lower surface of the base 96 rests on the upper surface ofthe platform 130, with the positioning tabs 114 oriented in thepositioning channels 134. In this arrangement, therefore, the peripheraledges of the leaflet are not pinched or otherwise compressed between theframing assembly halves. This helps reduce damage to the leaflet whichmay be assembled in a prosthetic valve and implanted for use in apatient.

The leaflet framing assembly 24 with leaflet 28 mounted therein is thenplaced back into its previously indexed position under the deflectorassembly 26. The L-shaped clamp 86 is brought into contact with the sideof the base locator 132, and the clamping screws 88 tightened to securethe framing assembly 24 on the base 22.

At this point, the deflector 30 is elevated manually with the positionindicator 50 remaining stationary. The deflector 30 is then placedgently on the top of the leaflet 28 by manually lowering the shaft 52.The leaflet support 140 is then removed carefully from underneath theleaflet 28 which is allowed to deflect under the weight of the mass 54.The deflector 30 is elevated away from contact with the leaflet 28, andthe test is repeated several times to insure correct readout. Preferablythe leaflet 28 is deflected five times, and the readouts of the fourthand fifth deflections are then recorded.

Upon removal of the leaflet mounting frame 94, the leaflet 28 shouldstay with the frame by virtue of the needles 110 piercing the leaflettissue. If all seven of the needle tips are visible through the leaflettissue, then the leaflet 28 is removed from the mounting frame 94 byloosening the needle clamp screw 112 and pulling the needles 110 outfrom above. The leaflet 28, if useable, is then placed in its particulardeflection grouping and stored for later combination with similarleaflets to produce a heart valve.

If any of the needles 110 are not visible through the tissue, then themounting frame 94 is reinstalled onto the leaflet holder 126. Afterremoving the mounting frame 94 once again, the needle tips should bevisible through the leaflet 28. When all the needle tips are visiblethrough the leaflet 28, the mounting frame 94 is replaced on the leafletholder 126 and one or more deflection tests are repeated. The data fromthe second set of deflection tests are then used to select and classifythe leaflet for later grouping with other leaflets. After this secondtest, the leaflet 28 is removed from the mounting frame 94 and placed inits particular deflection grouping.

Exemplary Tissue Selection Methodology

Studies in the prior art have demonstrated there can be a significantvariation in the stress/strain curves from specimen to specimen ofpericardial tissue. Tests have also demonstrated that typical stressloading of glutaraldehyde-fixed pericardial tissue results in varyingstrains for different tissue samples, even from the same pericardiumsac. Moreover, leaflets may experience localized stresses within amitral valve of up to 1,000 kPa, with a typical high average range ofbetween 500 and 600 kPa Previous studies have shown that the averagestress/strain curve of leaflet tissue material non-linearly increasesuntil a particular stress is reached after which the curve isapproximately linear (the tissue stretches significantly more at lowloads). In general, tissue is significantly stiffer in the high stressregion, and is more flexible at low stresses.

FIG. 11 illustrates a typical stress-strain curve for pericardialtissue. It will be understood that the curve is exemplary for aparticular tissue fixed in a particular way. Other tissues may responddifferently, but the trends shown are generally seen in fixed bovinepericardium tissue. The curve shows a low elastic modulus of the tissueat low stresses under about 300 kPa, and an increasing modulus at higherstresses. The curve is generally linear above about 300 to 600 kPa Forpurposes of discussion, a high modulus region (HMR) of the curve isshown in FIG. 11 within which the stress/strain curve is generallylinear. The HMR is an approximation of an average high stress rangewithin a particular fixed bovine pericardium leaflet in an implantedheart valve. This approximate information can be combined with knowledgeof the operating conditions and valve size to design an appropriatedeflection test method. That is, the bulk tissue stress/strain curvealong with the valve size and assumed loading and boundary conditionscan be combined to predict a stress distribution in the leaflet. Thesize of the mass 54 in the illustrated exemplary test apparatus 20 (FIG.1), for example, is then selected to stress the leaflet into the HMR ofthe tissue. Understressing the leaflet during the test may not obtainoptimum results, and over-stressing the leaflet may damage it. Thus, forexample, a preferred stress level applied to glutaraldehyde-fixedpericardial tissue leaflets for a 29 mm CEP valve in the testerapparatus 20 has been found to be in the HMR of between 300 and 600 kPa

The present tissue deflection test addresses the observed variation inresulting strain in tissue leaflets when the applied load is similar topressure loading under physiological conditions. As mentionedpreviously, localized stresses on a leaflet in use may reach 1,000 kPa.Testing of leaflets within the tester 20 is preferably accomplishedusing a significantly lower stress level, while still sufficientlydeflecting the leaflet in the linear stress/strain region for usefulresults. Empirical testing or finite element stress analysis on specificleaflet material is desirably used to predict the probable stress-strainrelationship of individual leaflets. This preliminary testing oranalysis is then used to design the proper deflection test method, asdescribed herein.

The particular testing stress level, however, is also affected by thetype of test configuration. The needles 110 secure the edges of theleaflet 28 in a uniform circumferential array which simulates thesutures which attach the leaflet cusp within a heart valve prosthesis.In particular, the cusp 152 of the leaflet 28 is held stationary atdiscrete points defined by the needles 110, while the coapting edge 148remains free. The number of needles 110 should be sufficient to simulatethis edge connection of the leaflet in use, but not be too numerous asthe needles pierce through the tissue of the leaflet. Therefore, betweenat least five and nine, and preferably at least seven needles 110 asshown are adequate for a uniform framing configuration of the leafletwithout creating an inordinate number of holes therein. As the load isapplied by the deflector 30 the stress distribution within the leaflet28 will not be completely uniform because the leaflet is only held atdiscrete locations. Therefore the load applied must be carefully gauged,so as not to create undue levels of stress concentration in and aroundthe points at which the needles pierce through the leaflet tissue. Thestated range of between 300 and 600 kPa for glutaraldehyde-fixedpericardial tissue leaflets has been determined to be suitable whenusing seven needles as shown. Of course, other arrangements for framingthe leaflet are possible, such as using more than seven needles, and thestress range may be appropriately modified. Further, the stress range isnot determined solely with reference to the leaflet holding arrangement.Those of skill in the art will recognize the exemplary test apparatus isan attempt to simulate true stresses imposed on the leaflet, withcertain tradeoffs, including simplifying the test apparatus andminimizing the number of needles used.

The mass 54 for a 29 mm CEP leaflet is chosen to be approximately 100 gto set up stress levels of between 300 and 600 kPa in the leaflet. Themass 54 for other size valve leaflets are scaled from the 100 gram loadused for the 29 mm valve leaflet, as seen in Table I.

TABLE I Valve Leaflet Size Deflection Load (g) 25 mm  74 27 mm  87 29 mm100 31 mm 112

Additional testing may be performed to insure that the appropriate mass54 selected for various valve size leaflets imparts a stress in agenerally linear region of the tissue stress/strain curve. One exampleof such testing is to use an Instron tensile test tester in place of theposition indicator 50. The Instron Tensile tester can be used to varythe load on the leaflet 28 and a series of stress/strain curves can begenerated for each leaflet size. Based on these test results, theminimum load on the tissue leaflets for all sizes to ensure that thestress/strain response is in the linear regime is approximately 60grams.

Other means of categorizing leaflets may be used in conjunction with thepresently described deflection test. For example, selection ofindividual leaflets to be grouped with other leaflets in a heart valvehas been accomplished by the assignee of the present invention using aso-called “droop” test of the leaflets. That is, the leaflets arecantilevered over the end of a rod, or other structure, and the droop ofthe leaflet for different lengths of extension is observed. The drooptest can thus be generally termed an intrinsic loading test, whereinthere is no applied load and the leaflet deflects solely under its ownweight. The droop test is used to categorize leaflets, so that leafletswith similar droop characteristics can be put together for assembly intoa heart valve in an attempt to improve leaflet cooperation andcoaptation. The droop test in combination with the presently describeddeflection test is particularly useful in grouping individual leafletswith similar characteristics for assembly into a multi-leaflet valve.

Results for loading of leaflets for use in various size valves is givenin FIG. 9. After the leaflets were deflected five times in succession toaccount for conditioning or change in the Young's modulus, a finaldeflection comprising the last observed deflection or an average of thelast two observed deflections were recorded. FIG. 9 shows thedistribution of deflection values from the tissue deflection test. Thedeflection values for the leaflets measured ranged from 0.19 to 0.36with the majority grouped between 0.23 and 0.30.

To illustrate the effectiveness of the methods and apparatuses of thepresent invention relative to conventional tissue categorizingtechniques, the droop test and tissue deflection test of the presentinvention were applied to 169 leaflets. The leaflets tested fordeflection response in FIG. 9 were then categorized by droop value.FIGS. 10 a, 10 b, and 10 c show the population of leaflets categorizedby letters A, B and C based on droop characteristic. In general, theleaflets from Group A had the lowest deflection values with Group Bsomewhere between Group A and Group C. There is significant overlap ofdeflection values between categories A, B, and C.

In an exemplary embodiment, the deflection test described herein isfirst used to categorize a number of similarly shaped leaflets intosubgroups, such as is shown in FIG. 9. Subsequently, a droop test isperformed on a subgroup of leaflets within a predetermined deflectionrange, and only leaflets within an acceptable droop range from thatsubgroup are combined into a prosthetic heart valve. Alternatively, thedroop test may be performed first to obtain a number of subgroups, oneor more of which is then deflection tested to arrive at a selected groupof leaflets suitable for combining together in a prosthetic heart valve.

In an exemplary embodiment, the individual leaflets 28 are deflectiontested and leaflets are selected which produced a total deflection ofbetween 0.170 and 0.340″ for valve sizes of 25 to 31 mm. Furthermore,for reliability, it is preferred that only leaflets be used for whichthe fourth and fifth readouts differ within a predetermined range, forexample between plus or minus 0.003 inches.

To evaluate the effect of selecting and combining tissue leaflets in 29mm CEP valves, four valves were manufactured and tested. Two leafletswere selected to have similar deflection values. The third leafletdeflection value was varied from approximately 0.010″ to 0.040″ comparedto the other leaflets as shown in Table II.

TABLE II Valve Deflection of Deflection Number Leaflets 1 & 2 of Leaflet3 Δ Deflection 13559 0.298 0.310 0.012 13560 0.254 0.277 0.023 135610.238 0.269 0.031 13562 0.277 0.317 0.040

The valves listed in Table II were placed into a pulsatile flowsimulator, and testing performed per conventional protocol. Thedifferential pressure for the testing was 200 mm Hg per Food and DrugAdministration guidelines. The valve commissure deflection for eachvalve was measured as shown in Table III.

TABLE III Comm. 1 Comm. 2 Comm. 3 Aver- Actual Actual Actual age Std.Valve No. Cycle No. (mm) (mm) (mm) (mm) Dev. 13559 1 0.89 1.10 0.78 0.920.16 2 0.89 1.10 0.78 0.92 0.16 3 0.86 1.13 0.79 0.93 0.18 13560 1 1.051.39 1.21 1.22 0.17 2 1.02 1.39 1.23 1.21 0.19 3 1.05 1.42 1.23 1.230.19 13561 1 1.26 1.32 1.07 1.22 0.13 2 1.26 1.36 1.08 1.23 0.14 3 1.231.32 1.08 1.21 0.12 13562 1 1.07 1.32 0.84 1.08 0.24 2 1.07 1.32 0.821.07 0.25 3 1.05 1.36 0.84 1.08 0.26 Average 1.11 Std. Dev. 0.16

Proper coaptation was observed in valves 13559, 13560, and 13561, wherethe mismatch between leaflets 1 and 2 and leaflet 3 was less thanapproximately 0.030″. Thus, from this particular study, leaflets whichhave deflection values differing by less than approximately 0.030″ aresuitably grouped for combining in a heart valve. Of course, this testapplies to 29 mm CEP valves made from selected bovine pericardium, andthere are a variety of parameters which could alter the conclusionregarding acceptable deflection correlation. Furthermore, the conclusionwas based on measured valve commissure deflection, which is onepredictor of prolonged leaflet coaptation. A desirable selectionmethodology, therefore, is to obtain a collection of similarly sizedleaflets apply a load to each leaflet, observe the resulting strainresponse, and sort the leaflets based on their respective strainresponses. Additionally, the leaflets are preferably chemically fixedprior to testing and a droop test is used in conjunction with thedeflection test results.

The present invention additionally teaches a multi-leaflet bioprostheticheart valve with leaflets selected to have observed deflection responseswithin a certain range. The average deflection in the range depends on anumber of variables, as explained above, and the breadth of the rangemay depend on empirical test results of assembled valves, such as thecommissure deflection data included in Table III. In one exemplaryembodiment, however, a 29 mm multi-leaflet bioprosthetic CEP heart valvecomprising glutaraldehyde-fixed bovine pericardium tissue leafletsincludes at least two leaflets having a deflection of within 0.030inches as measured using the exemplary testing method and apparatus,with a mass sufficient to create stresses in the leaflets of between 300and 600 kPa.

It should be noted that the present invention is best suited forcategorizing and selecting leaflets having varying material propertiesfrom leaflet to leaflet, such as in bovine pericardium. Recent advancesin bioprosthetic materials enable manufacturers to produce leaflets bygrowing tissue on a matrix. Such material may also exhibitnonuniformities in individual leaflets and could be grouped and/orselected in accordance with the present invention. Another type oftissue for which the present invention may prove valuable in selectingleaflets is a composite or laminate substrate on which a cell growthcovering is formed. Alternatively, the present selection methods andapparatuses may be applicable to leaflets made from materials with moreuniform properties, such as synthetically fabricated or extrudedcollagen sheets. Though the bulk material properties of these lattermaterials may be more predictable, individual testing of leaflets isbelieved desirable to more accurately assess the subsequent dynamicresponse of the leaflets in use. In addition, testing of leaflets usinga setup which closely simulates the particular heart valve in which theleaflet will be used is desirable, in addition to the pre-existingknowledge of the material properties. For these more uniform leaflets,testing of a sample of leaflets from a specific manufactured batch maysuffice.

In closing it is to be understood that the embodiments of the inventiondisclosed herein are illustrative of the principles of the invention andthat other modifications may be employed which are within the scopethereof. Accordingly, the present invention is not limited to thatprecisely as shown and described in the specification.

1. A process for manufacturing an implantable heart valve comprising thesteps of: providing a collection of similarly sized leaflets; applying aload to each leaflet; observing the strain response in each leafletcaused by applying the load; sorting the leaflets into subgroups basedon their respective strain responses such that the leaflets in eachsubgroup each have a strain response within a predetermined range; and,attaching only leaflets from a single subgroup to the heart valve suchthat when fluid pressure is applied to the implantable heart valve theleaflets thereon will exhibit similar strain response.
 2. The process ofclaim 1, wherein the step of providing a collection includes providing acollection of natural tissue leaflets.
 3. The process of claim 2,further including the step of chemically fixing the leaflets prior totesting.
 4. The process of claim 2, wherein the step of providing acollection of natural tissue leaflets includes providing a collection ofbovine pericardium leaflets.
 5. The process of claim 1, wherein the stepof providing a collection of leaflets includes providing a collection ofextruded collagen leaflets.
 6. The process of claim 1, wherein the stepof applying a load comprises applying a load sufficient to create anaverage stress in at least some of the leaflets within a generallylinear, high modulus region of a stress/strain curve of the leafletmaterial.
 7. The process of claim 1, further including the step ofapplying a load for a predetermined number of times prior to observingthe strain response.
 8. The process of claim 7, wherein thepredetermined number is at least three.
 9. The process of claim 1,further including the steps of: performing an intrinsic load test on theleaflets; and sorting the leaflets based on the intrinsic load testresults.
 10. The process of claim 1, wherein the step of formingsubgroups of leaflets having a strain response within a predeterminedrange comprises a measuring a deflection of each leaflet resulting fromapplying a load thereto, and forming a subgroup of leaflets each havinga deflection within about 0.030 inches of the others.
 11. A process formanufacturing an implantable heart valve having multiple leaflets,comprising the steps of: mounting the leaflet in a framing assembly sothat portions which are to be sutured in the valve are held stationary,wherein the leaflet defines a cusp edge and a coapted edge generallyopposite the cusp edge, and the framing assembly includes an uppermember and a lower member, the lower member having a recess forreceiving at least the cusp edge of the leaflet, the upper member beingshaped to mate over the recess, and the framing assembly defining acavity circumscribed by the recess, the step of mounting includingpositioning the leaflet in the recess and piercing the leaflet cusp edgewith needles extending between and supported from movement by the upperand lower members, to hold at least the cusp edge of the leafletstationary; applying a load to the leaflet in a location adapted tosimulate a point at which an average load is applied in the valve;sensing the resulting strain in the leaflet; sorting the leaflets intosubgroups based on their respective strain responses such that theleaflets in each subgroup have a strain response within a predeterminedrange; and, attaching only leaflets from a single subgroup to the heartvalve.
 12. The process of claim 11, wherein the step of applying a loadcomprises applying a mechanical deflector to an upper surface of theleaflet over the cavity.
 13. The process of claim 11, further includingthe step of recording the sensed strain.
 14. The process of claim 13,further including applying a load at least twice before recording thesensed strain.
 15. The process of claim 14, further including the stepof performing a droop test on the leaflet by extending the leaflet overthe end of a structure, and observing the resulting droop of theextended end of the leaflet.
 16. The process of claim 15, furtherincluding testing a second leaflet and correlating the results of thedroop tests and applied load tests for the two leaflets.
 17. The processof claim 11, wherein the leaflet is made of a leaflet material, and thestep of applying a load comprises applying a load sufficient to stressthe leaflet within a generally linear high modulus region of astress/strain curve of the leaflet material.
 18. The process of claim11, wherein the step of applying a load comprises applying a loadsufficient to stress the leaflet between 300 and 600 kPa.
 19. Theprocess of claim 1, wherein the heart valve comprises a wireformdefining alternating commissures and arcuate cusps, the cusp edge ofeach prosthetic leaflet being attached along a wireform cusp, whereinthe commissure portions of the prosthetic leaflets terminate inoutwardly extending tabs that each attach to a wireform commissure, andwherein tabs from adjacent leaflets are attached together at each of thewireform commissures.
 20. The process of claim 19, wherein the tabs fromadjacent leaflets extend outward between spaced wires of the wireformcommissure, and wherein inserts are provided around which the adjacentleaflet tabs wrap and are secured, the inserts being size larger thanthe distance that the wires of the wireform commissure are spaced apartso as to maintain the leaflet tabs on the outside of the wireformcommissure.